The research team, with Edward W. Hook III and Jodie A. Dionne as lead authors, conducted a multicenter, double-blind, randomized study on a large cohort of patients. The goal was to determine whether the three-dose regimen offered a superior clinical benefit compared to a single dose in patients with early latent syphilis.

Participants were randomly divided into two groups: one group received a single injection of benzathine penicillin G and two placebo injections (saline solution), while the other group received three injections of benzathine penicillin G, all administered at weekly intervals. Patients were then followed for an extended period, with the results analysis based on treatment success, defined by a decrease in blood antibody titers (expressed as VDRL or RPR titers) at 12 months.

Results: Is a single dose of Benzathine Penicillin G enough?
The study's results showed that, in terms of therapeutic success, there was no statistically significant difference between the two groups. Patients who received a single dose showed a treatment success rate comparable to that of the group who received three doses. This suggests that for early latent syphilis, a single injection of penicillin might be just as effective as the three-dose regimen, contrary to current clinical guidelines in many regions.

Implications for public health
The implications of this discovery are potentially enormous. Reducing the treatment from three doses to a single dose would offer numerous benefits:

Increased patient adherence. Many patients fail to complete the three-injection course due to various factors, such as inconvenience, cost, or difficulty returning to the clinic. A single-dose treatment would eliminate this barrier, significantly increasing the likelihood that patients complete the therapy.

Reduced healthcare costs. A shorter treatment regimen would result in lower costs for healthcare systems, both in terms of medication and clinical resources and staff time.

Simplified clinical management. Simplifying the treatment protocol would make patient management easier, especially in resource-limited settings.

The study's authors conclude that the single-dose regimen of benzathine penicillin G was shown to be non-inferior to the three-dose regimen for the treatment of early latent syphilis. These findings could lead to a revision of global clinical guidelines and represent a fundamental step toward a more efficient and accessible approach to managing this disease.

Although the results are promising, the researchers emphasize the importance of further studies to confirm this data in diverse populations and to explore long-term effectiveness, particularly in preventing late and rare sequelae such as neurosyphilis. This study, however, paves the way for a future where syphilis treatment could become simpler and more effective for everyone.

Bibliography

Centers for Disease Control and Prevention (CDC). (2021). Syphilis: A Pocket Guide for Providers. CDC, Division of STD Prevention.

Dionne, J. A., Batteiger, T. A., & Hook III, E. W. (2024). Revisiting the Treatment of Syphilis: Are We on the Cusp of Change? Clinical Infectious Diseases, 78(4), 589-591. DOI: 10.1093/cid/ciaa1622.

Donati G.18 Giu 2008 Human Papilloma Virus e altre malattie sessualmente trasmesse (MST) un reale problema di comunicazione Scienzaonline

Donati G.17 Dic 2003 Emergenza Malattie Sessualmente Trasmesse Scienzaonline

Ghanem, K. G., & Hook III, E. W. (2023). Syphilis. The Lancet, 401(10383), 1251-1262. DOI: 10.1016/S0140-6736(22)02547-4.

Hook III, E. W., Dionne, J. A., Workowski, K., McNeil, C. J., Taylor, S. N., Batteiger, T. A., Dombrowski, J. C., et al. (2025). One Dose versus Three Doses of Benzathine Penicillin G in Early Syphilis. The New England Journal of Medicine, 393(9), 869-878. DOI: 10.1056/NEJMoa2401802.

Workowski, K. A., & Bolan, G. A. (2015). Sexually Transmitted Diseases Treatment Guidelines, 2015. Morbidity and Mortality Weekly Report (MMWR) Recommendations and Reports, 64(RR-03), 1-137. Centers for Disease Control and Prevention (CDC).

World Health Organization (WHO). (2016). WHO guidelines for the treatment of Treponema pallidum (syphilis). World Health Organization, Department of Reproductive Health and Research.

*Board Member, SRSN (Roman Society of Natural Science)
Past Editor-in-Chief Italian Journal of Dermosurgery